a safety and efficacy study of oral cladribine in subjects with relapsing-remitting multiple sclerosis (rrms)

Conditions: Multiple Sclerosis, Relapsing-Remitting

Summary: the purpose of the study is to determine if cladribine tablets are a safe and effective treatment for relapsing-remitting multiple sclerosis (rrms).

this is a randomized, double-blind, three-arm, placebo-controlled, multi-center study. the study includes a pre-study evaluation period (up to 28 days prior to the start of treatment); an initial treatment period from week 1 to 48; and a re-treatment period during week 49 to 96. during the initial treatment period (week 1 to 48), eligible subjects are equally randomized by a central randomization system to receive either a) cladribine at a low dose (0.875 milligram per kilogram per course \[mg/kg/course\] for two courses plus placebo for two courses); b) cladribine at a high dose (0.875 mg/kg/course for four courses); or c) placebo (four courses). during the re-treatment period (weeks 49 to 96), subjects received either a) cladribine at a low dose (0.875 mg/kg/course for two courses); or b) placebo (two courses). for all randomized subjects, there is a rescue option of treatment with rebif® (interferon beta-1a 44 microgram (mcg) given subcutaneously three times a week), if the subject experienced more than one qualifying relapse, and/or experienced a sustained increase in their edss score of greater than or equal to (\>=) 1 point, or \>=1.5 points if baseline edss score is 0, (over a period of three months or greater), during a calendar year beginning at week 24. to maintain the blind, there is a treating physician who view clinical laboratory results and assess adverse events and safety information, and an independent blinded evaluating physician who will perform neurological exams. a central neuroradiology center, also blinded to treatment, will assess magnetic resonance imaging (mri) evaluations.

Eligibility criteria:
inclusion criteria: * male or female, between 18 and 65 years of age (inclusive, at time of informed consent) * has definite ms according to the mcdonald criteria * has relapsing-remitting disease with 1 or more relapses within 12 months prior to study day 1 * must have been clinically stable and not has a relapse within 28 days prior to study day 1 * has mri consistent with ms at the pre-study evaluation according to the fazekas criteria * has a edss score from 0 to 5.5, inclusive * weighed between 40-120 kilogram (kg), inclusive * if female, she must: 1. be post-menopausal or surgically sterilized; or 2. uses a hormonal contraceptive, intra uterine device, diaphragm with spermicide, or condom with spermicide, for the duration of the study; and 3. be neither pregnant nor breast-feeding * if male, he must be willing to use contraception to avoid pregnancies * be willing and able to comply with study procedures for the duration of the study * voluntarily provides written informed consent, and for united states of america (usa) sites only, a subject authorization under health insurance portability and accountability act (hipaa) exclusion criteria: * has secondary progressive ms (spms) or primary progressive ms (ppms) * prior use of disease modifying drugs (dmds) within the last 3 months, or 2 or more prior treatment failures with dmds on the basis of efficacy * has significant leukopenia (white blood cell count less than 0.5 times the lower limit of normal of the central laboratory) within 28 days prior to study day 1 * has received cladribine, mitoxantrone, total lymphoid irradiation, myelosuppressive therapy, campath-1h, cyclophosphamide, azathioprine, methotrexate or natalizumab * has received oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days prior to study day 1 * has compromised immune function or infection * has received oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days prior to study day 1 * has received cytokine-based therapy, intravenous immunoglobulin therapy, or plasmapheresis within 3 months prior to study day 1 * has platelet and absolute neutrophil counts below the lower limit of normal range within 28 days prior to study day 1 * has prior or current history of malignancy * has a history of persistent anemia, leukopenia, neutropenia, or thrombocytopenia after immunosuppressive therapy * has systemic disease that, in the opinion of the investigator, might interfere with subject safety, compliance or evaluation of the condition under study (for example, insulin-dependent diabetes, lyme disease, clinically significant cardiac, hepatic, or renal disease, human immunodeficiency virus, or human t-cell lymphotrophic virus type-1) * has a psychiatric disorder that, in the opinion of the investigator, was unstable or would preclude safe participation in the study * has allergy or hypersensitivity to gadolinium, to cladribine or any of its excipients * has used any investigational drug or experimental procedure within 6 months prior to study day 1